Annals of Oncology 7:997-1003, 1996
© 1996 European Society for Medical Oncology
review-article |
High-dose chemotherapy in germ-cell tumors
1Department of Medical Oncology, Centre Léon Bérard Lyon
2Department of Medicine, Centre Val d'Aurelle Montpellier
3Department of Biostatistics, Institut Gustave-Roussy Villejuif, France
Correspondence to: J. P. Droz, MD Department of Medical Oncology Centre Léon Bérard 28, rue Laennec 69008 Lyon, France
The majority of patients with advanced-stage germ-cell tumor are curable by cisplatin-based chemotherapy, but about 10% of those in the good-risk and 30%–50% in the poor-risk groups will experience relapse. Patients in first relapse have a 60% chance of entering a second complete remission and a 15%–25% probability that it will be durable. Regimens of high-dose chemotherapy with hematopoietic stem-cell support have been developed specifically for this patient population: they are usually based on combinations of etoposide, cyclophosphamide, ifosfamide and, originally, double-dose cisplatin or, nowadays, high-dose carboplatin. The role of high-dose chemotherapy was studied initially in salvage and later in first-line treatment. Four hundred thirtysix patients who received high-dose salvage chemotherapy have been reported, 96 (22%) of whom have obtained longterm complete remissions. Prognostic factors for outcome were disease status (absolute refractory, refractory or sensitive diseases), primary tumor site, response to prior chemotherapy and serum hCG levels prior to high-dose treatment. Patients with no adverse prognostic factors have a greater than 50% chance of cure after high-dose treatment. Patients with refractory disease did not benefit from high-dose chemotherapy. A randomized European trial is ongoing to evaluate prospectively the role of high-dose chemotherapy in comparison to standard ifosfamide-based salvage treatment.
In first-line consolidation treatment of poor-risk non-seminomatous germ-cell tumors, the results of phase II trials with carboplatin-based high-dose therapy are in favor of a survival impact when compared to historical controls. A prospective randomized trial is ongoing in the US to study the role of carboplatin-based high-dose consolidation treatment. The only prospective trial comparing a cisplatin-based high-dose treatment to standard chemotherapy failed to demonstrate any survival advantage for the high-dose procedure in this setting. New developments include the use of repeated cycles of high-dose chemotherapy with peripheral blood stem-cell support and the introduction of paclitaxel, a new active drug in this disease, and other non-cross-resistant cytotoxic agents in high-dose combination regimens.
developmental therapeutics, germ-cell tumors, high-dose chemotherapy, paclitaxel, prognostic factors